The purpose of this randomized, multi-site, clinical trial is to determine whether intensive therapy consisting of cholesterol-lowering statin drugs plus apheresis to cleanse the blood of low-density lipoprotein (LDL) cholesterol is more effective than statin therapy alone in reducing plaque volume in heart arteries of patients who have already suffered an acute coronary syndrome (ACS). The study will also investigate whether this intensive approach can help increase the presence of endothelial progenitor cells (EPC), stem cells that have been shown to reduce CV events in ACS patients. This study has II phases and FDA approval for phase II has been received.

Change in the total atheroma volume within at least 20mm of the target coronary artery from baseline to 12 weeks post-PCI. The measurement will be done via IVUS-VH. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

IVUS-VH allows for the identification of discrete plaque components using radiofrequency backscatter data. The technology can visualize the coronary artery wall and measure atherosclerosis volume.

Drug: Atorvastatin

80mg daily oral dose of Atorvastatin to lower LDL in blood.

Device: LDL-apheresis

The device proposed for use in this study is the LIPOSORBER LA-15 System, manufactured by Kaneka Pharma America LLC. The Liposorber separates plasma from whole blood, then removes LDL from the plasma, recombines the plasma and blood cells, and returns the blood into the patient's body; the procedure typically takes about 3 hours. The procedure provides an immediate reduction in a patient's lipid levels. A single apheresis treatment can lower LDL by more than 80%, but levels return to baseline within 3 weeks.

IVUS-VH allows for the identification of discrete plaque components using radiofrequency backscatter data. The technology can visualize the coronary artery wall and measure atherosclerosis volume.

Drug: Atorvastatin

80mg daily oral dose of Atorvastatin to lower LDL in blood.

Detailed Description:

Using statins to lower blood cholesterol, and specifically LDL, is well established as a long-term strategy to reduce CVs and even death. But the most intensive pharmacologic lipid-lowering therapy with statins, though proven superior to standard dose regimens, is still associated with an unacceptably high rate of recurrent CV events early after an ACS. This study hypothesizes that for ACS patients undergoing percutaneous coronary intervention (PCI), intensive lipid-lowering therapy consisting of statins and LDL-apheresis (ILLT) will significantly reduce the total coronary atheroma volume of vulnerable plaque and augment mobilization of peripherally circulating EPC colony forming units, compared to guideline statin monotherapy (SMT). ILLT will lead to fewer CV events for these patients.

Patients presenting at two VA sites with ACS will be screened and consented before undergoing uncomplicated PCI (balloons or stents) and intravascular ultrasound with virtual histology (IVUS-HS). They will then be randomized into the ILLT arm or SMT arm of the study. The ILLT group will receive one treatment of LDL-apheresis plus a daily oral 80mg dose of Atorvastatin; the SMT group will only get the Atorvastatin. Patients will again undergo IVUS-HS 12 weeks after enrollment to measure atheroma volume; EPC level will also be checked.

The four-year duration of the study includes 24 months of accrual, six months of follow-up, and 12 months of study closure and data analysis. A two-sample t-test of mean difference with 90% power and 0.65 Cohen's D effect size provides a total sample size estimate of 102. Counting 20% drop-out rate, the sample size increases to 128.

The recent FDA recommendations regarding the design of the study has been included in the revised study protocol:

The first stage will enroll 30 patients with a 2:1 randomization favoring LDL-apheresis. the safety data will be submitted to the FDA.

The enrollment of the second stage of the study will be contingent to the recommendations of the FDA.

Referred for clinically-indicated, non-emergent (the procedure is not required to be performed within 3 hours after patient presentation) coronary angiography and PCI with IVUS-VH of target coronary artery for ACS

Successful placement of two large bore IV cannulas in bilateral upper extremities

Fasting ( 12 hrs) LDL 100mg/dl while on 80mg Atorvastatin or equivalent dose of other statin, performed at time of admission or 3 months prior to PCI.

Exclusion Criteria:

Known allergy to aspirin, clopidogrel, statins, or iodinated contrast

Positive pregnancy test, planning to become pregnant, or breast-feeding

Coexisting conditions that limit life expectancy to less than six months or affect patient compliance

Uncontrolled fasting ( 12 hrs) triglyceride levels ( 500mg/dl)

Already participating in an investigational device or drug study

History of heparin induced thrombocytopenia (HIT)

Persons with estimated GFR less than 60 ml/min if they are diabetic; persons with eGFR of less than 45 ml/min if they are not diabetic

ST-elevation myocardial infarction at admission

Abnormal liver function test (LFT) at time of admission or 3 month prior to PCI with abnormal LFT defined as any liver transaminases (ALT or AST) 3 times the upper limit of the normal laboratory reference

Pre-PCI or post-PCI left ventricular ejection fraction <25% by echo or cardiac catheterization done after admission

Persons whose hemoglobin is less than 9 grams following the index PCI/IVUS procedure, or who experience a drop in hemoglobin of greater than or equal to 2 grams following the procedure

Not able to comply with study protocol as determined by the investigators

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01004406